He Yan, Ke Hongqin, Zhu Jianyong, Yuan Xin, Li Hongliang, Wu Wenwen, Yang Shuman, Yu Huibin
Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China.
Front Pharmacol. 2025 May 9;16:1542554. doi: 10.3389/fphar.2025.1542554. eCollection 2025.
To construct and validate a risk prediction model for patients with meropenem-induced liver injury (MiLI).
A retrospective case-control study was conducted to collect data on inpatients treated with meropenem at Shiyan People's Hospital, Hubei, China from January 2018 to December 2022; this study served as the model construction dataset. Univariate analysis and multiple logistic regression analysis were employed to identify the related factors for MiLI, and a nomogram risk prediction model for MiLI was constructed. The recognition ability and prediction accuracy of the model were evaluated using the receiver operating characteristic (ROC) and calibration curves. The clinical efficacy was assessed via the decision curve analysis (DCA). The internal validation was performed using the bootstrap method, and external validation was conducted based on an external dataset from Shiyan Taihe Hospital between October 2021 and December 2023.
A total of 1,625 individuals were included in the model construction dataset, of which 62 occurred MiLI. The external validation dataset included 1,032 cases, with 74 patients developing liver injury. Six variables were independent factors for MiLI and included in the final prediction model: being male (OR = 2.080, 95% CI: 1.050-4.123, = 0.036), ICU admission (OR = 8.207, 95% CI: 4.094-16.453, < 0.001), gallbladder disease (OR = 8.240, 95% CI: 3.605-18.832, < 0.001), baseline ALP (OR = 1.012, 95% CI: 1.004-1.019, = 0.004), GGT (OR = 1.010, 95% CI: 1.005-1.015, < 0.001), and PLT (OR = 0.997, 95% CI: 0.994-0.999, = 0.020). The statistic value for internal validation of the prediction model was 0.821; the sensitivity and specificity were 0.997 and 0.924, respectively. The statistic value of the prediction model in the model construction dataset was 0.837 (95% CI, 0.789-0.885), while in the external validation dataset was 0.851 (95% CI, 0.802-0.901). The -values of the calibration curve in the two datasets were 0.935 and 0.084, respectively.
Being male, ICU admission, gallbladder disease, higher levels of baseline ALP and GGT, and lower levels of baseline PLT were the risk factors for MiLI. The nomogram model built based on these factors demonstrated favorable performance in discrimination, calibration, clinical applicability, and internal-external validation. The nomogram model can assist clinicians in early identification of high-risk patients receiving meropenem, predicting the risk of MiLI, and ensuring safe medication practices.
构建并验证美罗培南诱导的肝损伤(MiLI)患者的风险预测模型。
进行一项回顾性病例对照研究,收集2018年1月至2022年12月在中国湖北省十堰市人民医院接受美罗培南治疗的住院患者的数据;本研究作为模型构建数据集。采用单因素分析和多因素逻辑回归分析确定MiLI的相关因素,并构建MiLI的列线图风险预测模型。使用受试者工作特征(ROC)曲线和校准曲线评估模型的识别能力和预测准确性。通过决策曲线分析(DCA)评估临床疗效。采用自抽样法进行内部验证,并基于十堰太和医院2021年10月至2023年12月的外部数据集进行外部验证。
模型构建数据集中共纳入1625例个体,其中62例发生MiLI。外部验证数据集包括1032例病例,74例患者发生肝损伤。六个变量是MiLI的独立因素并纳入最终预测模型:男性(OR = 2.080,95%CI:1.050 - 4.123,P = 0.036)、入住重症监护病房(ICU)(OR = 8.207,95%CI:4.094 - 16.453,P < 0.001)、胆囊疾病(OR = 8.240,95%CI:3.605 - 18.832,P < 0.001)、基线碱性磷酸酶(ALP)(OR = 1.012,95%CI:1.004 - 1.019,P = 0.004)、γ-谷氨酰转肽酶(GGT)(OR = 1.010,95%CI:1.005 - 1.015,P < 0.001)和血小板计数(PLT)(OR = 0.997,95%CI:0.994 - 0.999,P = 0.020)。预测模型的内部验证统计值为0.821;敏感性和特异性分别为0.997和0.924。预测模型在模型构建数据集中的统计值为0.837(95%CI,0.789 - 0.885),而在外部验证数据集中为0.851(95%CI,0.802 - 0.901)。两个数据集中校准曲线的P值分别为0.935和0.084。
男性、入住ICU、胆囊疾病、较高的基线ALP和GGT水平以及较低的基线PLT水平是MiLI的危险因素。基于这些因素构建的列线图模型在区分度、校准度、临床适用性以及内部和外部验证方面表现良好。列线图模型可协助临床医生早期识别接受美罗培南治疗的高危患者;预测MiLI的风险并确保安全用药。